Trehalose (D-glucose-α-1,1-α-D-glucose) is a disaccharide sugar that is prevalent throughout nature, but not found in mammals. Trehalose is an essential metabolite for mycobacteria, such as Mycobacterium tuberculosis (Mtb), and is responsible for millions of deaths yearly and is a major global health threat due to drug resistance. Because trehalose and its derivatives, such as O-acylated derivatives (e.g., trehalose mono- and dimycolate) are integral to Mtb physiology and pathogenesis, yet absent from the human host, trehalose metabolism may be a target for diagnostic and therapeutic applications.